Introduction In this article, we will discuss the causes and treatment of Alzheimer's disease (AD), a common neurodegenerative disease. We will begin by exploring the symptoms and different stages of development in AD. Next, we will delve into the underlying pathophysiology of the disease. Finally, we will examine the available drug treatments and lifestyle interventions that are employed to manage AD.
An Introduction to Alzheimer’s Disease AD is a progressive neurodegenerative disease with an insidious onset. It is the most common cause of dementia in the elderly population, manifesting as memory loss and difficulties with thinking, problem-solving or language. According to Alzheimer's Disease International (ADI), there are currently at least 50 million people with dementia worldwide, and by 2050 it is expected to reach 152 million, of which about 60-70% are Alzheimer's disease patients. The progress of AD mainly includes two clinical phases. The first stage is the pre-clinical stage. Patients in this stage usually present with mild cognitive impairment. However, they have no functional impairment in their daily activities and no clinical signs and symptoms of AD [1].
The second phase of Alzheimer's disease is known as the dementia stage, which consists of three levels: mild, moderate, and severe. In the mild stage, the primary characteristic is memory impairment. As the disease progresses to the moderate stage, individuals may experience difficulties in various cognitive domains, including work, learning, and social abilities. This can manifest as challenges in logical thinking, problem-solving, and numerical skills. Additionally, spatial awareness issues and the occurrence of seizures may be observed. Personality changes such as heightened excitement, irritability, or depression may also become apparent. In the severe stage of AD, individuals lose their ability to perform daily activities, struggle with communication and social interaction, and often experience stiffness or paralysis in their limbs. They may also develop urinary and bowel incontinence, necessitating long-term rest.
Figure 1. Medical animation shows the affected areas of the brain in each stage of Alzheimer's disease and the average duration for each stage. Image adapted from: https://seniordirectory.com/articles/info/what-are-the-three-stages-of-alzheimers-disease
Understanding the Causes of Alzheimer’s Diseases
AD is a group of heterogeneous diseases resulting from a combination of genetic, lifestyle and environmental factors. However, its exact cause has not been elucidated. Two main hypotheses of AD’s pathophysiology have been proposed by scholars. The first suggests that impaired cholinergic function is the primary causative agent of AD. The other suggests that AD is mainly related to amyloid plaque (AP) deposit, which can result in neuronal malfunction and cell death in the hippocampus area (a brain area involved in memory and planning) [2]. Numerous risk factors have been identified in AD research, including ageing, genetics, environmental factors, and medical factors. Ageing is a crucial risk factor, as most cases of AD tend to develop after the age of 65. Genetic factors also play a role, with mutations in genes such as Amyloid precursor protein (APP), presenilin-1 (PSEN-1), presenilin-2 (PSEN-2), or apolipoprotein E (ApoE) being associated with AD.
Managing Alzheimer's Disease Symptoms: Treatment Approaches and Strategies Currently, there is no known cure for AD, and therefore, the primary focus is on symptomatic treatment. Since AD is associated with decreased acetylcholine (ACh) synthesis and low cholinergic levels, Cholinesterase Inhibitors (AChEIs) are commonly used to treat AD. These medications work by inhibiting the degradation of ACh, thereby increasing its activity. Examples of AChEIs used in AD treatment include donepezil, rivastigmine, and galantamine. Additionally, N-methyl-D-aspartate (NMDA) antagonists, such as memantine, can be prescribed to prevent the over-activation of NMDA receptors and reduce excitotoxicity. Memantine is approved for treating moderate to severe AD, either as a standalone treatment or in combination with AChEIs. Vasodilators that enhance cerebral blood flow and brain cell metabolism may also be employed to slow down the progression of the disease. Treatment with these medications can lead to improvements in cognition, behaviour, and daily life skills.
As the disease advances, some patients may develop psychiatric symptoms. AD patients often experience negative emotions such as anger, guilt, frustration, worry, sadness, and a sense of social isolation. In such cases, antidepressants and antipsychotics may be prescribed, including medications like fluoxetine, paroxetine, citalopram, risperidone, and olanzapine. It is also important for families to encourage patients to engage in social and daily activities, maintain a healthy lifestyle, and promote a calm state of mind. If necessary, seeking support from a psychologist can be beneficial. This article is written by Weiyun Zhang, Queen Mary University of London, UK.
References
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Wang, Y., Liu, T., Ma, X., and Ding, F. (2022) 'Current perspectives on the genetics of Alzheimer's disease', Molecular Neurodegeneration, 17(1), 54. doi: 10.1186/s13024-022-00523-1